(Circulation. 1997;95:1242-1246.)
© 1997 American Heart Association, Inc.
Articles |
Prevalence of Heparin-Associated Antibodies Without Thrombosis in Patients Undergoing Cardiopulmonary Bypass Surgery
the Departments of Surgery (T.L.B., E.N.E., J.D.M.) and Anesthesiology (S.M.), the Cardeza Foundation for Hematologic Research (B.A.K., B.M., S.S.S.), and the Biostatistics Section (W.W.H.), Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pa; Departments of Medicine (G.A., D.B.C.) and Pathology and Laboratory Medicine (D.B.C.), University of Pennsylvania; Division of Pediatric Hematology (M.P.), Children's Hospital of Philadelphia; and the Immunology Department (J.A.), SERBIO, Gennervilliers, France.
Correspondence to John D. Mannion, MD, Thomas Jefferson University, Department of Surgery, 1025 Walnut St, Suite 607 College, Philadelphia, PA 19107.
Background Patients with cardiovascular disease almost invariably receive heparin before cardiopulmonary bypass surgery, which places them at risk of developing heparin-associated antibodies with a risk of thromboembolic complications. This study was designed to determine the prevalence of heparin-induced antibodies in patients before and after cardiopulmonary bypass surgery.
Methods and Results Plasma from 111 patients was tested before surgery and 5 days after surgery for heparin-dependent platelet-reactive antibodies with a 14C-serotonin–release assay (SRA) and for antibodies to heparin/platelet factor 4 complexes with an ELISA. Heparin exposure after surgery was minimized. Heparin-dependent antibodies were detected before surgery in 5% of patients with SRA and 19% of patients with ELISA. By the fifth postoperative day, there was a marked increase in patients positive on the SRA or ELISA (13% and 51%, respectively; P<.01 for each). Patients who had received heparin therapy earlier in their hospitalization were more likely to have a positive ELISA before surgery (35%; P=.017) and a positive ELISA (68%; P=.054) or SRA (30%; P=.002) after surgery. However, there was no difference in the prevalence of thrombocytopenia or thromboembolic events between the antibody-positive and -negative groups.
Conclusions Approximately one fifth of patients undergoing cardiopulmonary bypass surgery have heparin-induced platelet antibodies detectable before the procedure as a result of prior heparin exposure, and many more develop antibodies after surgery. The absence of an association between these antibodies and thromboembolic complications in this study may be, in part, attributable to careful avoidance of heparin after surgery. The high prevalence of heparin-induced antibodies in this setting suggests that these patients may be at risk of developing thrombotic complications with additional heparin exposure.
Key Words: cardiopulmonary bypass • heparin • platelets • thrombosis
This article has been cited by other articles:
 |
|
 |
|
  A. Greinacher and J. H. Levy HIT Happens: Diagnosing and Evaluating the Patient with Heparin-Induced Thrombocytopenia Anesth. Analg., August 1, 2008; 107(2): 356 - 358. [Full Text] [PDF]
|
|
|
|
|
|
M. P. Mullen, D. L. Wessel, K. C. Thomas, K. Gauvreau, E. J. Neufeld, F. X. McGowan Jr, and J. A. DiNardo The Incidence and Implications of Anti-Heparin-Platelet Factor 4 Antibody Formation in a Pediatric Cardiac Surgical Population Anesth. Analg., August 1, 2008; 107(2): 371 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fareed, R. L. Bick, G. Rao, S. Z. Goldhaber, A. Sasahara, H. L. Messmore, D. A. Happensteadt, and A. Nicolaides The Immunogenic Potential of Generic Version of Low-Molecular-Weight Heparins May Not be the Same as the Branded Products Clinical and Applied Thrombosis/Hemostasis, January 1, 2008; 14(1): 5 - 7. [PDF]
|
|
|
|
 |
|
 Z. I. Khalpey, R. B. Ganim, and J. D. Rawn Postoperative Care of Cardiac Surgery Patients Card. Surg. Adult, January 1, 2008; 3(2008): 465 - 486. [Full Text]
|
|
|
|
 |
|
 S. Suvarna, B. Espinasse, R. Qi, R. Lubica, M. Poncz, D. B. Cines, M. R. Wiesner, and G. M. Arepally Determinants of PF4/heparin immunogenicity Blood, December 15, 2007; 110(13): 4253 - 4260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Kerendi, V. H. Thourani, J. D. Puskas, P. D. Kilgo, M. Osgood, R. A. Guyton, and O. M. Lattouf Impact of Heparin-Induced Thrombocytopenia on Postoperative Outcomes After Cardiac Surgery Ann. Thorac. Surg., November 1, 2007; 84(5): 1548 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Demir, E. Duran, O. Yigitbasi, O. Vural, T. Kurum, M. Yuksel, B. Turgut, J. M. Walenga, and J. Fareed Incidence of Antiheparin-Platelet Factor 4 Antibodies and Heparin-Induced Thrombocytopenia in Turkish Patients Undergoing Cardiac Surgery Clinical and Applied Thrombosis/Hemostasis, July 1, 2007; 13(3): 279 - 284. [Abstract] [PDF]
|
|
|
|
 |
|
 T. E. Warkentin and J. W. Eikelboom Who Is (Still) Getting HIT? Chest, June 1, 2007; 131(6): 1620 - 1622. [Full Text] [PDF]
|
|
|
|
|
|
D. C. Kress, S. Aronson, M. L. McDonald, M. I. Malik, A. B. Divgi, A. J. Tector, F. X. Downey III, A. J. Anderson, M. Stone, and C. Clancy Positive Heparin-Platelet Factor 4 Antibody Complex and Cardiac Surgical Outcomes Ann. Thorac. Surg., May 1, 2007; 83(5): 1737 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mitchell, C. A. Riley, and B. Vahid Unusual Complication of Heparin-Induced Thrombocytopenia After Mitral Valve Surgery: Spontaneous Rupture of Spleen Ann. Thorac. Surg., March 1, 2007; 83(3): 1172 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Everett, R. Yeh, S. Y. Foo, D. Criss, E. M. Van Cott, M. Laposata, E. G. Avery, W. D. Hoffman, J. Walker, D. Torchiana, et al. Prevalence of Heparin/Platelet Factor 4 Antibodies Before and After Cardiac Surgery Ann. Thorac. Surg., February 1, 2007; 83(2): 592 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wan, M. Warner, B. DeVarennes, P. Ergina, R. Cecere, and K. Lachapelle Clinical Presentation, Temporal Relationship, and Outcome in Thirty-Three Patients With Type 2 Heparin-Induced Thrombocytopenia After Cardiotomy Ann. Thorac. Surg., July 1, 2006; 82(1): 21 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schenk, A. El-Banayosy, W. Prohaska, L. Arusoglu, M. Morshuis, W. Koester-Eiserfunke, L. Kizner, E. Murray, P. Eichler, R. Koerfer, et al. Heparin-induced thrombocytopenia in patients receiving mechanical circulatory support J. Thorac. Cardiovasc. Surg., June 1, 2006; 131(6): 1373 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. de Maistre, Y. Gruel, and D. Lasne Diagnosis and management of heparin-induced thrombocytopenia: [Le diagnostic et le traitement de la thrombopenie induite par l'heparine]. Can J Anesth, June 1, 2006; 53(6_suppl): S123 - S134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rauova, L. Zhai, M. A. Kowalska, G. M. Arepally, D. B. Cines, and M. Poncz Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications Blood, March 15, 2006; 107(6): 2346 - 2353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Jackson, W. J. Neilson, M. Lary, P. Baay, K. Web, and G. P. Clagett Delayed-Onset Heparin-Induced Thrombocytopenia and Thrombosis After Intraoperative Heparin Anticoagulation: Four Case Reports Vascular and Endovascular Surgery, January 1, 2006; 40(1): 67 - 70. [Abstract] [PDF]
|
|
|
|
|
|
E. Bennett-Guerrero, T. F. Slaughter, W. D. White, I. J. Welsby, C. S. Greenberg, H. El-Moalem, and T. L. Ortel Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1567 - 1572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. U. Jones, J. B. Muhlestein, K. W. Jones, D. G. Renlund, T. L. Bair, T. J. Bunch, B. D. Horne, D. L. Lappe, J. L. Anderson, and D. B. Doty Early Postoperative Use of Unfractionated Heparin or Enoxaparin is Associated with Increased Surgical Re-Exploration for Bleeding Ann. Thorac. Surg., August 1, 2005; 80(2): 518 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rauova, M. Poncz, S. E. McKenzie, M. P. Reilly, G. Arepally, J. W. Weisel, C. Nagaswami, D. B. Cines, and B. S. Sachais Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia Blood, January 1, 2005; 105(1): 131 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kumar, D. A. Hoppensteadt, M. M. Prechel, R. B. Deddish, and J. M. Walenga Prevalance of Heparin-Dependent Platelet-Activating Antibodies in Preterm Newborns After Exposure to Unfractionated Heparin Clinical and Applied Thrombosis/Hemostasis, October 1, 2004; 10(4): 335 - 339. [Abstract] [PDF]
|
|
|
|
|
|
A. F. Merry, P. J. Raudkivi, N. G. Middleton, J. M. McDougall, P. Nand, B. P. Mills, B. J. Webber, C. M. Frampton, and H. D. White Bivalirudin versus heparin and protamine in off-pump coronary artery bypass surgery Ann. Thorac. Surg., March 1, 2004; 77(3): 925 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Koster and T. Fischer Management of Patients with Heparin-Induced Thrombocytopenia During Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2003; 7(4): 411 - 416. [Abstract] [PDF]
|
|
|
|
|
|
T. E. Warkentin and A. Greinacher Heparin-induced thrombocytopenia and cardiac surgery Ann. Thorac. Surg., December 1, 2003; 76(6): 2121 - 2131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Leo and S. Winteroll Laboratory Diagnosis of Heparin-Induced Thrombocytopenia and Monitoring of Alternative Anticoagulants Clin. Vaccine Immunol., September 1, 2003; 10(5): 731 - 740. [Full Text] [PDF]
|
|
|
|
|
|
T. E. Warkentin and A. Greinacher Heparin-induced thrombocytopenia and cardiac surgery Ann. Thorac. Surg., August 1, 2003; 76(2): 638 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Edwards, J. K. Hamby, and N. K. Worrall Successful use of argatroban as a heparin substitute during cardiopulmonary bypass: heparin-induced thrombocytopenia in a high-risk cardiac surgical patient Ann. Thorac. Surg., May 1, 2003; 75(5): 1622 - 1624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Carrier, D. Robitaille, L. P. Perrault, M. Pellerin, P. Page, R. Cartier, and D. Bouchard Heparin versus danaparoid in off-pump coronary bypass grafting: Results of a prospective randomized clinical trial J. Thorac. Cardiovasc. Surg., February 1, 2003; 125(2): 325 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Nuttall, W. C. Oliver Jr, P. J. Santrach, R. D. McBane, D. B. Erpelding, C. L. Marver, and K. J. Zehr Patients with a History of Type II Heparin-Induced Thrombocytopenia with Thrombosis Requiring Cardiac Surgery with Cardiopulmonary Bypass: A Prospective Observational Case Series Anesth. Analg., February 1, 2003; 96(2): 344 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Francis, G. J. Palmer III, R. Moroose, and A. Drexler Comparison of bovine and porcine heparin in heparin antibody formation after cardiac surgery Ann. Thorac. Surg., January 1, 2003; 75(1): 17 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Alving How I treat heparin-induced thrombocytopenia and thrombosis Blood, January 1, 2003; 101(1): 31 - 37. [Full Text] [PDF]
|
|
|
|
|
|
Z. Q. Li, W. Liu, K. S. Park, B. S. Sachais, G. M. Arepally, D. B. Cines, and M. Poncz Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody Blood, February 15, 2002; 99(4): 1230 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hambleton, L. L. Leung, and M. Levi Coagulation: Consultative Hemostasis Hematology, January 1, 2002; 2002(1): 335 - 352. [Abstract] [Full Text]
|
|
|
|
|
|
M. P. Reilly, S. M. Taylor, N. K. Hartman, G. M. Arepally, B. S. Sachais, D. B. Cines, M. Poncz, and S. E. McKenzie Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through Fc{gamma}RIIA Blood, October 15, 2001; 98(8): 2442 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Konkle, T. L. Bauer, G. Arepally, D. B. Cines, M. Poncz, S. McNulty, R. N. Edie, and J. D. Mannion Heparin-induced thrombocytopenia: bovine versus porcine heparin in cardiopulmonary bypass surgery Ann. Thorac. Surg., June 1, 2001; 71(6): 1920 - 1924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aouifi, P. Blanc, V. Piriou, O. H. Bastien, P. Ffrench, M. Hanss, and J.-J. Lehot Cardiac surgery with cardiopulmonary bypass in patients with type II heparin-induced thrombocytopenia Ann. Thorac. Surg., February 1, 2001; 71(2): 678 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Koster, M. Loebe, R. Sodian, E. V. Potapov, R. Hansen, J. Muller, F. Mertzlufft, G. J. Crystal, H. Kuppe, and R. Hetzer Heparin antibodies and thromboembolism in heparin-coated and noncoated ventricular assist devices J. Thorac. Cardiovasc. Surg., February 1, 2001; 121(2): 0331 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. McCrae, J. B. Bussel, P. M. Mannucci, G. Remuzzi, and D. B. Cines Platelets: An Update on Diagnosis and Management of Thrombocytopenic Disorders Hematology, January 1, 2001; 2001(1): 282 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Warkentin, J.-A. I. Sheppard, P. Horsewood, P. J. Simpson, J. C. Moore, and J. G. Kelton Impact of the patient population on the risk for heparin-induced thrombocytopenia Blood, September 1, 2000; 96(5): 1703 - 1708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Arepally, S. Kamei, K. S. Park, K. Kamei, Z. Q. Li, W. Liu, D. L. Siegel, W. Kisiel, D. B. Cines, and M. Poncz Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies Blood, March 1, 2000; 95(5): 1533 - 1540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Koster, H. Kuppe, G. J. Crystal, and F. Mertzlufft Cardiovascular Surgery Without Cardiopulmonary Bypass in Patients with Heparin-Induced Thrombocytopenia Type II Using Anticoagulation with Recombinant Hirudin Anesth. Analg., February 1, 2000; 90(2): 292 - 292. [Full Text] [PDF]
|
|
|
|
|
|
D. E. Wallis, R. Quintos, W. Wehrmacher, and H. Messmore Safety of Warfarin Anticoagulation in Patients With Heparin-Induced Thrombocytopenia Chest, November 1, 1999; 116(5): 1333 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bacsi, R. De Palma, G.P. Visentin, J. Gorski, and R.H. Aster Complexes of Heparin and Platelet Factor 4 Specifically Stimulate T Cells From Patients With Heparin-Induced Thrombocytopenia/Thrombosis Blood, July 1, 1999; 94(1): 208 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Pouplard, M.-A. May, S. Iochmann, J. Amiral, A.-M. Vissac, M. Marchand, and Y. Gruel Antibodies to Platelet Factor 4–Heparin After Cardiopulmonary Bypass in Patients Anticoagulated With Unfractionated Heparin or a Low-Molecular-Weight Heparin : Clinical Implications for Heparin-Induced Thrombocytopenia Circulation, May 18, 1999; 99(19): 2530 - 2536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Wallis, B. E. Lewis, H. Messmore, and W. H. Wehrmacher State-of-the-Art Review : Heparin-induced Thrombocytopenia and Thrombosis Syndrome Clinical and Applied Thrombosis/Hemostasis, July 1, 1998; 4(3): 160 - 163. [PDF]
|
|